Document Report Card

ID: ALA1126030

Journal: J Med Chem

Title: Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents: X-ray crystal structure assisted design.

Authors: Thompson WJ, Fitzgerald PM, Holloway MK, Emini EA, Darke PL, McKeever BM, Schleif WA, Quintero JC, Zugay JA, Tucker TJ.

Abstract: By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.

CiteXplore: 1588551

DOI: 10.1021/jm00088a003